Yi X, Ding L, Jin Y, Ni C, Wang W
Eye Institute, Eye and E.N.T. Hospital, Shanghai Medical University, P. R. China.
Int J Radiat Oncol Biol Phys. 1994 May 15;29(2):393-6. doi: 10.1016/0360-3016(94)90296-8.
Retinoblastoma is the most common intraocular malignant tumor in children. Previous investigations have reported that buthionine sulfoximine (BSO) can deplete intracellular glutathione (GSH) by specific inhibition and increase cellular radiosensitivity. The toxic effects, GSH depletion and radiosensitivity of BSO on retinoblastoma cells are reported in this paper. GSH content of retinoblastoma cell lines Y-79, So-Rb50 and retinoblastoma xenograft is 2.7 +/- 1.3 x 1.0(-12) mmol/cell, 1.4 +/- 0.2 x 1.0(-12) mmol/cell, and 2.8 +/- 1.2 mumol/g, respectively. The ID50 of BSO on Y-79 and So-Rb50 in air for 3 h exposure is 2.5 mM and 0.2 mM, respectively. GSH depletion by 0.1 mM BSO for 24 h on Y-79 cells and 0.01 mM BSO for 24 h on So-Rb50 cells is 16.35%, and 4.7% of control. GSH depletion in tumor and other organ tissues in retinoblastoma-bearing nude mice after BSO administration is differential. GSH depletion after BSO exposure in Y-79 cells in vitro decreases the Do value of retinoblastoma cells. The SER of 0.01 mM and 0.05 mM BSO for 24 h under the hypoxic condition is 1.21 and 1.36, respectively. Based on these observations, the authors conclude that BSO toxicity on retinoblastoma cells depends on the characteristics of cell line and that BSO can increase hypoxic retinoblastoma cells' radiosensitivity in vitro. Further study of BSO radiosensitization on retinoblastoma in vivo using nude mouse xenograft is needed.
视网膜母细胞瘤是儿童最常见的眼内恶性肿瘤。既往研究报道，丁硫氨酸亚砜胺（BSO）可通过特异性抑制作用消耗细胞内谷胱甘肽（GSH）并增加细胞放射敏感性。本文报道了BSO对视网膜母细胞瘤细胞的毒性作用、GSH消耗及放射敏感性。视网膜母细胞瘤细胞系Y-79、So-Rb50及视网膜母细胞瘤异种移植物的GSH含量分别为2.7±1.3×1.0（-12）mmol/细胞、1.4±0.2×1.0（-12）mmol/细胞及2.8±1.2μmol/g。BSO对Y-79和So-Rb50在空气中暴露3小时的半数抑制浓度（ID50）分别为2.5 mM和0.2 mM。0.1 mM BSO作用24小时对Y-79细胞、0.01 mM BSO作用24小时对So-Rb50细胞的GSH消耗分别为对照的16.35%和4.7%。给予BSO后，视网膜母细胞瘤荷瘤裸鼠肿瘤及其他器官组织中的GSH消耗存在差异。体外BSO暴露后Y-79细胞内GSH消耗降低了视网膜母细胞瘤细胞的Do值。在缺氧条件下，0.01 mM和0.05 mM BSO作用24小时的增敏增强比（SER）分别为1.21和1.36。基于这些观察结果，作者得出结论，BSO对视网膜母细胞瘤细胞的毒性取决于细胞系的特征，且BSO可在体外增加缺氧视网膜母细胞瘤细胞的放射敏感性。需要进一步研究BSO对视网膜母细胞瘤裸鼠异种移植物的体内放射增敏作用。
